The association of acute rheumatic fever and acute glomerulonephritis with antecedent Group A streptococcal infections has been well documented. Cross-reactions between membranes from different types and strains of Group A streptococci and human heart, kidney, and brain tissue have been shown. Although the antigen of the streptococcal membrane that cross-reacts with human sarcolemmal sheath has been purified, little is known about the composition of this bacterial membrane. The major objective of this study is to initiate an in-depth analysis of the Group A streptococcal membrane with particular emphasis on the relations of antigenic and chemical composition to pathogenicity. Initially, the antigenic and protein composition of membranes from two strains, one from a "rheumatogenic" strain and the other from a "nephritogenic" strain, will be characterized by quantitative immunoelectrophoresis (e.g., crossed immunoelectrophoresis) and SDS-polyacrylamide gel techniques. This will include zymogram methods and specific assays for membrane components. The effect of growth phase and cultural conditions (medium, pH, cAMP, and serum) on the over-all composition and expression of specific antigens will be examined. This will enable us to optimize conditions for isolation of these antigens. It may also yield insight into the mechanism of pathogenesis of this organism. Comparisons of membranes from a number of strains associated with rheumatic fever versus membranes from strains associated with acute glomerulonephritis will be carried out. This expansion to a larger number of strains will also include comparison of skin and throat strains. The effects of mouse passage and rotation in blood on production of novel or important antigens will be examined in strains selected from those characterized above.